The nature and role of the neurogenic influence on cerebrovascular tone is the subject of considerable current interest. There is evidence for both a sympathetic vasoconstrictor and a vasodilator innervation of pial vessels. These two systems have been unequivocably demonstrated in isolated cerebral blood vessels and found to have puzzling features. Multidisciplinary in vitro methodology offers a powerful analytical approach to the definition of these neuroeffector mechanisms. Included in this proposal are the measurement of vascular smooth muscle tone in pial vessels as small as 100 micrometers, electrophysiology of cerebral vascular smooth muscle, biochemistry of the nerve terminal and histology and histochemistry of the vascular wall. Amongst the hypotheses to be tested are that many of the unique features of the sympathetic innervation of rabbit cerebral arteries can be attributed to an unusual alpha-adrenergic receptor, that the atropine-resistant vasodilator innervation of cerebral vessels is mediated by acetylcholine acting either by inhibiting adjacent sympathetic neurons or on an unusual vascular smooth muscle mechanisms and that there is marked species variation in the relative importance and properties of the two types of innervating systems.